COVID-19 can cause some individuals to experience chronic symptoms. Rates and predictors of chronic COVID-19 symptoms are not fully elucidated. To examine occurrence and patterns of post-acute ...sequelae of SARS-CoV2 infection (PASC) symptomatology and their relationship with demographics, acute COVID-19 symptoms and anti-SARS-CoV-2 IgG antibody responses. A multi-stage observational study was performed of adults (greater than or equal to18 years) from 5 US states. Participants completed two rounds of electronic surveys (May-July 2020; April-May 2021) and underwent testing to anti-SARS-CoV-2 nucleocapsid protein IgG antibody testing. Latent Class Analysis was used to identify clusters of chronic COVID-19 symptoms. Overall, 390 adults (median 25%ile, 75%ile age: 42 31, 54 years) with positive SARS-CoV-2 antibodies completed the follow-up survey; 92 (24.7%) had greater than or equal to1 chronic COVID-19 symptom, with 11-month median duration of persistent symptoms (range: 1-12 months). The most common chronic COVID-19 symptoms were fatigue (11.3%), change in smell (9.5%) or taste (5.6%), muscle or joint aches (5.4%) and weakness (4.6%). There were significantly higher proportions of greater than or equal to1 persistent COVID-19 symptom (31.5% vs. 18.6%; Chi-square, P = 0.004), and particularly fatigue (15.8% vs. 7.3%, P = 0.008) and headaches (5.4% vs. 1.0%, P = 0.011) in females compared to males. Chronic COVID-19 symptoms were also increased in individuals with greater than or equal to6 acute COVID-19 symptoms, Latent class analysis revealed 4 classes of symptoms. Latent class-1 (change of smell and taste) was associated with lower anti-SARS-CoV-2 antibody levels; class-2 and 3 (multiple chronic symptoms) were associated with higher anti-SARS-CoV-2 antibody levels and more severe acute COVID-19 infection. Individuals with SARS-CoV-2 infection commonly experience chronic symptoms, most commonly fatigue, changes in smell or taste and muscle/joint aches. Female sex, severity of acute COVID-19 infection, and higher anti-SARS-CoV-2 IgG levels were associated with the highest risk of having chronic COVID-19 symptoms.
Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence in the United States are still emerging.
To elucidate SARS-CoV-2 seroprevalence and symptom onset in a culturally ...linked community across 5 states in the United States.
This cross-sectional study included adults (aged ≥18 years) recruited from the orthodox Jewish community across 5 states (California, Connecticut, Michigan, New Jersey, and New York) in 3 geographically distinct areas of the United States between May 13 and July 6, 2020. Participants completed an online survey and underwent SARS-CoV-2 antibody testing.
Seroprevalence and date of symptom onset of SARS-CoV-2.
Overall, 9507 adults (mean SD age, 39.6 15.0 years; 3777 39.7% women) completed the SARS-CoV-2 survey, of whom 6665 (70.1%) had immunoglobin G anti-SARS-CoV-2 antibody levels assessed. A high seroprevalence of SARS-CoV-2 antibodies was observed across all communities, with the highest proportion of positive testing observed in New Jersey (1080 of 3323 32.5%) and New York (671 of 2196 30.6%). Most individuals with a positive SARS-CoV-2 immunoglobin G antibody test reported a date of symptom-onset between March 9 and March 31, 2020 (California: 135 of 154 87.7%; Connecticut: 32 of 34 94.1%; Michigan: 44 of 50 88.0%; New Jersey: 964 of 1168 82.5%; New York: 571 of 677 84.3%). This start date was coincident with the Jewish festival of Purim, celebrated March 9 to 10, 2020, with extensive intracommunity spread in the weeks following (mean and mode of peak symptom onset, March 20, 2020), occurring in the absence of strong general and culture-specific public health directives.
This cross-sectional study of orthodox Jewish adults across the US found that socioculturally bound communities experienced early parallel outbreaks in discrete locations, notably prior to substantive medical and governmental directives. Further research should clarify optimal national, local, community-based, and government policies to prevent outbreaks in social and cultural communities that traditionally gather for holidays, assemblies, and festivals.
The complex relationship between clinical manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and individual immune responses is not fully elucidated.
To examine phenotypes ...of symptomatology and their relationship with positive anti–SARS-CoV-2 IgG antibody responses.
An observational study was performed of adults (≥18 years) from 5 US states. Participants completed an electronic survey and underwent testing to anti–SARS-CoV-2 nucleocapsid protein IgG antibody between May and July 2020. Latent class analysis was used to identify characteristic symptom clusters.
Overall, 9507 adults (mean age, 39.6 ± 15.0 years) completed the survey; 6665 (70.1%) underwent antibody testing for anti–SARS-CoV-2 IgG. Positive SARS-CoV-2 antibodies were associated with self-reported positive SARS-CoV-2 nasal swab result (bivariable logistic regression; odds ratio 95% CI, 5.98 4.83-7.41), household with 6 or more members (1.27 1.14-1.41) and sick contact (3.65 3.19-4.17), and older age (50-69 years: 1.55 1.37-1.76; ≥70 years: 1.52 1.16-1.99), but inversely associated with female sex (0.61 0.55-0.68). Latent class analysis revealed 8 latent classes of symptoms. Latent classes 1 (all symptoms) and 4 (fever, cough, muscle ache, anosmia, dysgeusia, and headache) were associated with the highest proportion (62.0% and 57.4%) of positive antibodies, whereas classes 6 (fever, cough, muscle ache, headache) and 8 (anosmia, dysgeusia) had intermediate proportions (48.2% and 40.5%), and classes 3 (headache, diarrhea, stomach pain) and 7 (no symptoms) had the lowest proportion (7.8% and 8.5%) of positive antibodies.
SARS-CoV-2 infections manifest with substantial diversity of symptoms, which are associated with variable anti–SARS-CoV-2 IgG antibody responses. Prolonged fever, anosmia, and receiving supplemental oxygen therapy had strongest associations with positive SARS-CoV-2 IgG.
Background COVID-19 can cause some individuals to experience chronic symptoms. Rates and predictors of chronic COVID-19 symptoms are not fully elucidated. Objective To examine occurrence and patterns ...of post-acute sequelae of SARS-CoV2 infection (PASC) symptomatology and their relationship with demographics, acute COVID-19 symptoms and anti-SARS-CoV-2 IgG antibody responses. Methods A multi-stage observational study was performed of adults (≥18 years) from 5 US states. Participants completed two rounds of electronic surveys (May-July 2020; April-May 2021) and underwent testing to anti-SARS-CoV-2 nucleocapsid protein IgG antibody testing. Latent Class Analysis was used to identify clusters of chronic COVID-19 symptoms. Results Overall, 390 adults (median 25%ile, 75%ile age: 42 31, 54 years) with positive SARS-CoV-2 antibodies completed the follow-up survey; 92 (24.7%) had ≥1 chronic COVID-19 symptom, with 11-month median duration of persistent symptoms (range: 1–12 months). The most common chronic COVID-19 symptoms were fatigue (11.3%), change in smell (9.5%) or taste (5.6%), muscle or joint aches (5.4%) and weakness (4.6%). There were significantly higher proportions of ≥1 persistent COVID-19 symptom (31.5% vs. 18.6%; Chi-square, P = 0.004), and particularly fatigue (15.8% vs. 7.3%, P = 0.008) and headaches (5.4% vs. 1.0%, P = 0.011) in females compared to males. Chronic COVID-19 symptoms were also increased in individuals with ≥6 acute COVID-19 symptoms, Latent class analysis revealed 4 classes of symptoms. Latent class-1 (change of smell and taste) was associated with lower anti-SARS-CoV-2 antibody levels; class-2 and 3 (multiple chronic symptoms) were associated with higher anti-SARS-CoV-2 antibody levels and more severe acute COVID-19 infection. Limitations Ambulatory cohort with less severe acute disease. Conclusion Individuals with SARS-CoV-2 infection commonly experience chronic symptoms, most commonly fatigue, changes in smell or taste and muscle/joint aches. Female sex, severity of acute COVID-19 infection, and higher anti-SARS-CoV-2 IgG levels were associated with the highest risk of having chronic COVID-19 symptoms.
A completely regioselective and highly stereoselective palladium‐catalyzed intramolecular hydroarylation of arenesulfonyl ynamines to benzothiazoles was developed. The presence of an ...electron‐withdrawing group on the triple bond of the sulfonyl ynamine was crucial for the success of the reaction and our mechanistic studies suggest an alkyne‐directed 5‐exo‐dig cyclization pathway. The products easily underwent photoinduced rearrangement to 3‐amino‐1‐benzothiophene‐1,1‐diones (up to 35 % yields after two steps).
A completely regioselective and highly stereoselective palladium‐catalyzed intramolecular hydroarylation of arenesulfonyl ynamines to benzothiazoles was developed. Our mechanistic studies suggest an alkyne‐directed 5‐exo‐dig cyclization pathway of the process. The products easily underwent photoinduced rearrangement to 3‐amino‐1‐benzothiophene‐1,1‐diones (up to 35 % yields after two steps).
High-resolution peripheral quantitative computed tomography (HR-pQCT) has the potential to improve radiographic progression determination in clinical trials and longitudinal observational studies. ...The goal of this work was to describe the current state of research presented at Outcome Measures in Rheumatology (OMERACT) 2016 and ensuing future directions outlined during discussion among attendees.
At OMERACT 2016, SPECTRA (Study grouP for xtrEme-Computed Tomography in Rheumatoid Arthritis) introduced efforts to (1) validate the HR-pQCT according to OMERACT guidelines, focusing on rheumatoid arthritis (RA), and (2) find alternatives for automated joint space width (JSW) analysis. The Special Interest Group (SIG) was presented to patient research partners, physicians/researchers, and SIG leaders followed by a 40-min discussion on future directions.
A consensus definition for RA erosion using HR-pQCT was demonstrated through a systematic literature review and a Delphi exercise. Histopathology and perfusion studies were presented that analyzed the true characteristics of cortical breaks in HR-pQCT images, and to provide criterion validity. Results indicate that readers were able to discriminate between erosion and small vascular channels. Moderate reliability (ICC 0.206-0.871) of direct erosion size measures was shown, which improved (> 0.9) only when experienced readers were considered. Quantification of erosion size was presented for scoring, direct measurement, and volumetric approaches, as well as a reliability exercise for direct measurement. Three methods for JSW measurement were compared, all indicating excellent reproducibility with differences at the extremes (i.e., near-zero and joint edge thickness).
Initial reports on HR-pQCT are promising; however, to consider its use in clinical trials and longitudinal observational studies, it is imperative to assess the responsiveness of erosion measurement quantification.
A promising bone graft substitute is porous titanium. Porous titanium, produced by selective laser melting (SLM), can be made as a completely open porous and load-bearing scaffold that facilitates ...bone regeneration through osteoconduction. In this study, the bone regenerative capacity of porous titanium is improved with a coating of osteostatin, an osteoinductive peptide that consists of the 107-111 domain of the parathyroid hormone (PTH)-related protein (PTHrP), and the effects of this osteostatin coating on bone regeneration were evaluated in vitro and in vivo. SLM-produced porous titanium received an alkali-acid-heat treatment and was coated with osteostatin through soaking in a 100 nM solution for 24 h or left uncoated. Osteostatin-coated scaffolds contained ∼0.1 μg peptide/g titanium, and in vitro 81% was released within 24 h. Human periosteum-derived osteoprogenitor cells cultured on osteostatin-coated scaffolds did not induce significant changes in osteogenic (alkaline phosphatase ALP, collagen type 1 Col1, osteocalcin OCN, runt-related transcription factor 2 Runx2), or angiogenic (vascular endothelial growth factor VEGF) gene expression; however, it resulted in an upregulation of osteoprotegerin (OPG) gene expression after 24 h and a lower receptor activator of nuclear factor kappa-B ligand (RankL):OPG mRNA ratio. In vivo, osteostatin-coated, porous titanium implants increased bone regeneration in critical-sized cortical bone defects (p=0.005). Bone regeneration proceeded until 12 weeks, and femurs grafted with osteostatin-coated implants and uncoated implants recovered, respectively, 66% and 53% of the original femur torque strength (97±31 and 77±53 N·mm, not significant). In conclusion, the osteostatin coating improved bone regeneration of porous titanium. This effect was initiated after a short burst release and might be related to the observed in vitro upregulation of OPG gene expression by osteostatin in osteoprogenitor cells. Long-term beneficial effects of osteostatin-coated, porous titanium implants on bone regeneration or mechanical strength were not established here and may require optimization of the pace and dose of osteostatin release.
A dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) ...infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor have clade C HIV-1-specific CD4+ T cell epitopes, likely a vital component of an effective global HIV-1 vaccine, been identified.
Intracellular cytokine staining was conducted on 373 subjects with chronic, untreated clade C infection to assess interferon-gamma (IFN-gamma) responses by CD4+ T cells to pooled Gag peptides and to determine their association with viral load and CD4 count. Gag-specific IFN-gamma-producing CD4+ T cell responses were detected in 261/373 (70%) subjects, with the Gag responders having a significantly lower viral load and higher CD4 count than those with no detectable Gag response (p<0.0001 for both parameters). To identify individual peptides targeted by HIV-1-specific CD4+ T cells, separate ELISPOT screening was conducted on CD8-depleted PBMCs from 32 chronically infected untreated subjects, using pools of overlapping peptides that spanned the entire HIV-1 clade C consensus sequence, and reconfirmed by flow cytometry to be CD4+ mediated. The ELISPOT screening identified 33 CD4+ peptides targeted by 18/32 patients (56%), with 27 of the 33 peptides located in the Gag region. Although the breadth of the CD4+ responses correlated inversely with viral load (p = 0.015), the magnitude of the response was not significantly associated with viral load.
These data indicate that in chronic untreated clade C HIV-1 infection, IFN-gamma-secreting Gag-specific CD4+ T cell responses are immunodominant, directed at multiple distinct epitopes, and associated with viral control.
The effective use of don't cares requires solving several theoretical and practical problems. The theoretical problems are caused by a need to have all tools in a methodology use a consistent ...semantics of don't cares, so as to guarantee correctness of the final implementation. Several common meanings of "don't care" will be considered, and their respective conditions for design correctness will be derived. The main theoretical result shows that in existing design languages, the following three desirable properties are mutually inconsistent: unrestricted use of non-Boolean values (e.g., X), implementing a large design one partition at a time, and assurance of correctness of the final implementation. A practical solution to this problem involves several issues: specifying don't cares in a language description, deriving them during high-level synthesis, and optimizing logic in their presence. Experimental results showing the impact of don't cares on logic quality are presented.
Be careful with don't cares Brand, D.; Bergamaschi, R.A.; Stok, L.
Proceedings of IEEE International Conference on Computer Aided Design (ICCAD),
1995
Conference Proceeding
It is commonly expected that any correct implementation can replace its specification inside a larger design without violating the correctness of the whole design. This property (called ...replaceability) is automatically satisfied in the absence of don't cares because "correctness" by definition implies that specification and implementation compute the identical function. However don't cares allow an implementation to compute a different function, and thus make it difficult to ensure replaceability. Whether this problem occurs depends on the exact meaning of "don't care" and the associated definition of "correctness". We will consider three meanings of "don't care" and for each give conditions under which correct implementations may replace their specifications.
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